Abstract
Introduction: UPLC coupled with a high-resolution mass analyzer i.e, Q-TOF analyzer with electrospray ionization (ESI) source using collision-induced dissociation (CID) method was applied to study the characteristic product ions of azilsartan protonated ion.
Method: The experimental results of high-resolution mass spectra explained the elemental compositions of product ions accurately and reasonable fragmentation pathways were proposed for azilsartan protonated ions. Calculated mass error in parts per million (ppm) for molecular ions and product ions and results of mass error found from this study from 0.2 ppm to 3.5 ppm.
Result: The characteristic fragmentation pathways were helpful to analyze and interpret the stability and possible degradation pathway of the parent ion.
Conclusion: The present study explains the significant role of high-resolution mass spectrometry in the structural analysis of the protonated ion of azilsartan.
Graphical Abstract
[1]
Kaushik, D.; Kaur, J.; Paul Kaur, V.; Saini, B.; Bansal, Y.; Bansal, G. Forced degradation, LC–UV, MSn and LC–MS–TOF studies on azilsartan: Identification of a known and three new degradation impurities. J. Pharm. Biomed. Anal., 2016, 120, 202-211.
[http://dx.doi.org/10.1016/j.jpba.2015.12.027] [PMID: 26752083]
[http://dx.doi.org/10.1016/j.jpba.2015.12.027] [PMID: 26752083]
[2]
Swain, D.; Patel, P.N.; Palaniappan, I.; Sahu, G.; Samanthula, G. Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium. Rapid Commun. Mass Spectrom., 2015, 29(15), 1437-1447.
[http://dx.doi.org/10.1002/rcm.7235] [PMID: 26147484]
[http://dx.doi.org/10.1002/rcm.7235] [PMID: 26147484]
[3]
Ebeid, W.M.; Elkady, E.F.; El-Zaher, A.A.; El-Bagary, R.I.; Patonay, G. Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: Application to degradation kinetics. Anal. Bioanal. Chem., 2014, 406(26), 6701-6712.
[http://dx.doi.org/10.1007/s00216-014-8085-0] [PMID: 25190009]
[http://dx.doi.org/10.1007/s00216-014-8085-0] [PMID: 25190009]
[4]
Al-Majed, A.A.; Bakheit, A.H.H.; Al-Muhsin, A.; Al-Kahtani, H.M.; Abdelhameed, A.S. Azilsartan medoxomil. Profiles of drug substances, excipients and related methodology; Elsevier: Amsterdam, 2020, 45, pp. 1-39.
[http://dx.doi.org/10.1016/bs.podrm.2019.10.001]
[http://dx.doi.org/10.1016/bs.podrm.2019.10.001]
[5]
Kher, M.; Bhatt, V.; Jani, A.; Sheth, N. Development and validation of stability indicating chromatographic methods for determination of Azilsartan Medoxomil in pharmaceutical formation. Anal. Chem. Lett., 2020, 10(3), 387-401.
[http://dx.doi.org/10.1080/22297928.2020.1784788]
[http://dx.doi.org/10.1080/22297928.2020.1784788]
[6]
Zhou, W.; Zhou, Y.; Sun, L.; Zou, Q.; Wei, P.; Ouyang, P. Structural elucidation of potential impurities in Azilsartan bulk drug by HPLC. J. AOAC Int., 2014, 97(6), 1552-1562.
[http://dx.doi.org/10.5740/jaoacint.14-022] [PMID: 25632433]
[http://dx.doi.org/10.5740/jaoacint.14-022] [PMID: 25632433]
[7]
Tian, Z.; Liu, F.; Li, D.; Fernie, A.R.; Chen, W. Strategies for structure elucidation of small molecules based on LC–MS/MS data from complex biological samples. Comput. Struct. Biotechnol. J., 2022, 20, 5085-5097.
[http://dx.doi.org/10.1016/j.csbj.2022.09.004]
[http://dx.doi.org/10.1016/j.csbj.2022.09.004]
[8]
Shandilya, D.K.; Joseph, P.E.; Kantamreddi, V.S.S. Interpretation of full scan atmospheric pressure ionization Mass Spectra (MS) and collision induced dissociation fragmentation spectra (MS/MS) of small organic molecules – a mini review. Sys. Rev. Pharm., 2017, 8(1), 48-51.
[http://dx.doi.org/10.5530/srp.2017.1.9]
[http://dx.doi.org/10.5530/srp.2017.1.9]
[9]
Kind, T.; Fiehn, O. Advances in structure elucidation of small molecules using mass spectrometry. Bioanal. Rev., 2010, 2(1-4), 23-60.
[http://dx.doi.org/10.1007/s12566-010-0015-9] [PMID: 21289855]
[http://dx.doi.org/10.1007/s12566-010-0015-9] [PMID: 21289855]
[10]
Defossez, E.; Bourquin, J.; von Reuss, S.; Rasmann, S.; Glauser, G. Eight key rules for successful data-dependent acquisition in mass spectrometry-based metabolomics. Mass Spectrom. Rev., 2021, 18.
[http://dx.doi.org/10.1002/mas.21715] [PMID: 34145627]
[http://dx.doi.org/10.1002/mas.21715] [PMID: 34145627]
[11]
Silva, P.J.; Prather, K.A. Interpretation of mass spectra from organic compounds in aerosol time-of-flight mass spectrometry. Anal. Chem., 2000, 72(15), 3553-3562.
[http://dx.doi.org/10.1021/ac9910132] [PMID: 10952542]
[http://dx.doi.org/10.1021/ac9910132] [PMID: 10952542]
[12]
Zaikin, V.G.; Halket, J.M. Derivatization in mass spectrometry--8. Soft ionization mass spectrometry of small molecules. Eur. J. Mass Spectrom., 2006, 12(2), 79-115.
[http://dx.doi.org/10.1255/ejms.798] [PMID: 16723751]
[http://dx.doi.org/10.1255/ejms.798] [PMID: 16723751]
[13]
Grześkowiak, T.; Zgoła-Grześkowiak, A.; Rusińska-Roszak, D.; Zaporowska-Stachowiak, I.; Jeszka-Skowron, M. Fragmentation studies of selected drugs utilized in palliative care. Eur. J. Mass Spectrom., 2018, 24(6), 420-436.
[http://dx.doi.org/10.1177/1469066718812459] [PMID: 30400754]
[http://dx.doi.org/10.1177/1469066718812459] [PMID: 30400754]
[14]
Iwan, V.; Grotemeyer, J. Elucidating the fragmentation mechanism of protonated Lewis A Trisaccharide using MS n CID. Eur. J. Mass Spectrom., 2021, 27(6), 256-265.
[http://dx.doi.org/10.1177/14690667211069033] [PMID: 34951325]
[http://dx.doi.org/10.1177/14690667211069033] [PMID: 34951325]
[15]
Nicolescu, T.O. Interpretation of mass spectra. Mass Spectrometry; IntechOpen, 2017.
[http://dx.doi.org/10.5772/intechopen.68595]
[http://dx.doi.org/10.5772/intechopen.68595]
[16]
McLAFFERTY, F.W.; TUREČEK, F. Interpretation of Mass Spectra, 4th ed; University Science Books: Sausalito, 1993, p. 371.
[17]
Smith, R.M.; Busch, K.L. Understanding Mass Spectra: A basic approach; Wiley-Interscience: New York, 1999, p. 290.
[19]
Ham, B.M. Even electron mass spectrometry with biomolecule applications; Wiley: New Jersey, 2008, p. 440.
